Efficacy, safety, and potential industry bias in using deoxycholic acid for submental fat reduction - A systematic review and meta-analysis of randomized clinical trials

Inocencio, Gabriel Santiago Giuglio; Meneses-Santos, Daniela; Costa, Marcelo Dias Moreira de Assis; Vieira, Walbert A.; Almeida, Vinicius Lima de; Rodrigues, Renata Prata Cunha Bernardes; Rode, Sigmar de Mello; Paranhos, Luiz Renato

doi:10.1016/j.clinsp.2023.100220

person Gabriel Santiago Giuglio Inocencio

performed the preparation · data collection · analysis · wrote the first draft of the manuscript · commented on previous versions of the manuscript · read and approved the final manuscript · conception and design of the study

schoolPostgraduate Program in Dentistry, Faculdade de Odontologia, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil

0000-0001-5168-7920

person Daniela Meneses-Santos

performed the preparation · data collection · analysis · commented on previous versions of the manuscript · read and approved the final manuscript · conception and design of the study

schoolDivision of Morphology, Centro de Ciências da Saúde e Biológicas, Universidade Federal de Sergipe, SE, Brazil

0000-0002-8898-9508

person Marcelo Dias Moreira de Assis Costa

performed the preparation · data collection · analysis · commented on previous versions of the manuscript · read and approved the final manuscript · conception and design of the study

schoolPostgraduate Program in Dentistry, Faculdade de Odontologia, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil

0000-0001-9148-3674

person Walbert A. Vieira

performed the preparation · data collection · analysis · commented on previous versions of the manuscript · read and approved the final manuscript · conception and design of the study

schoolDepartment of Restorative Dentistry, Endodontics Division, Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas (UNICAMP), Piracicaba, SP, Brazil

0000-0001-8872-2865

person Vinicius Lima de Almeida

wrote the first draft of the manuscript · commented on previous versions of the manuscript · read and approved the final manuscript · conception and design of the study

schoolPostgraduate Program in Dentistry, Faculdade de Odontologia, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil

0000-0002-2135-1040

person Renata Prata Cunha Bernardes Rodrigues

commented on previous versions of the manuscript · read and approved the final manuscript · conception and design of the study

schoolDivision of Preventive and Community Dentistry, Faculdade de Odontologia, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil

0000-0002-9721-6435

person Sigmar de Mello Rode

commented on previous versions of the manuscript · read and approved the final manuscript · conception and design of the study

schoolDepartment of Dental Materials and Prothesis, Instituto de Ciência e Tecnologia, Universidade Estadual Paulista Júlio de Mesquita Filho, São José dos Campos, SP, Brazil

0000-0002-4261-4217

person Luiz Renato Paranhos *

commented on previous versions of the manuscript · read and approved the final manuscript · conception and design of the study

schoolDivision of Preventive and Community Dentistry, Faculdade de Odontologia, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil

0000-0002-7599-0120

person* Corresponding author.
E-mail address: paranhos.lrp@gmail.com (L.R. Paranhos).

Declaration of Competing Interest

The authors declare no conflicts of interest.

Authors	Sponsorship	Industry	Conflicts of interest	Last author (adviser)
Ascher et al.²¹	√	Bayer HealthCare and KYTHERA Biopharmaceuticals Inc.	Two authors are employees of Bayer HealthCare, and one author is a former employee and current consultant of KYTHERA Biopharmaceuticals Inc.	B. Havlickova
Rzany et al.²²	√	Bayer HealthCare AG and KYTHERA Biopharmaceuticals Inc.	The sponsors were responsible for the study design, coordination, and compilation of the data provided by the researchers.	B. Havlickova
Humphrey et al.²³	√	KYTHERA Biopharmaceuticals Inc.	Two authors worked as researchers for Kythera Biopharmaceuticals Inc.; three authors worked as speakers, consultants, and members of the advisory board of Kythera Biopharmaceuticals Inc.; one author was a hired employee of Kythera Biopharmaceuticals Inc. during this study; and one author was a hired employee and shareholder of Kythera Biopharmaceuticals Inc. during this trial. Also, one author was a Senior Medical Director; one author was vice-president of clinical development, biostatistics, and data management; and one author was a Medical Director of Kythera Biopharmaceuticals Inc., where they hired employees, shareholders, and stock option holders during this study. Two authors are current employees of Sienna Biopharmaceuticals Inc., Westlake Village, California, USA.	F. C. Beddingfield
Jones et al.²⁴	√	KYTHERA Biopharmaceuticals Inc.	Four authors received fees, payments, or other compensation for working in this study; one author bought shares after concluding the trial; six authors were employees of Kythera Biopharmaceuticals Inc. during this study; and one author is an employee of Evidence Scientific Solutions, Philadelphia, PA, USA, and provided medical writing assistance supported by Kythera Biopharmaceuticals Inc.	F. C. Beddingfield
Glogau et al.²⁵	√	KYTHERA Biopharmaceuticals Inc.	The authors received payment as researchers for this clinical trial and had previously received a subsidy, consulting fees, travel aid, and payment to develop educational material and speeches for Kythera Biopharmaceuticals Inc.	B. Bowen

Outcome	ATX concentration	No. of studies	RR (95% CI)	I² test
Edema	2 mg	3	2.06 (1.78 – 2.39)	0%
Eritema	1 mg	2	1.80 (1.36 – 2.39)	0%
	2 mg	5	1.61 (1.35 – 1.93)	0%
Fibrosis	1 mg	2	10.04 (3.64 – 27.68)	0%
	2 mg	5	9.74 (6.08 – 15.61)	0%
Headache	2 mg	3	2.07 (1.26 – 3.41)	0%
Hematoma	1 mg	2	1.27 (1.07 – 1.52)	0%
	2 mg	5	1.06 (0.98 – 1.14)	0%
Nasopharyngitis	2 mg	2	0.88 (0.57 – 1.36)	0%
Nodule	2 mg	3	5.66 (3.16 – 10.14)	20%
Numbness	1 mg	2	21.78 (9.04 – 52.44)	0%
	2 mg	5	13.09 (9.48 – 18.08)	0%
Pain	1 mg	2	3.04 (2.46 – 3.77)	0%
	2 mg	5	2.38 (1.86 – 3.04)	73%
Paresthesia	2 mg	3	3.25 (2.04 – 5.18)	50%
Pruritus	2 mg	3	2.00 (1.35 – 2.97)	0%
SLRS improvement or no change	1 mg	2	1.00 (0.94 – 1.05)	9%
	2 mg	5	1.01 (0.98 – 1.04)	0%
Swelling	2 mg	3	2.22 (1.76 – 2.79)	0%

[TFN1] The studies were classified as (U) uncertain when it was impossible to assess with certainty the sponsorship status due to missing information even after contacting the authors via e-mail, (x) not sponsored when the authors informed the study was not financially supported by companies, and (√) sponsored when the authors informed the study had some financial support from companies. The sponsorship status was defined when the authors mentioned it in the main text or the acknowledgment section of the studies, regardless of the type of sponsorship (financial support, provision of products, etc.). Both reviewers previously discussed all items to ensure consistency in their interpretation.